Modifications of the iron–neuromelanin system in Parkinson's disease

Authors

  • Mauro Fasano,

    1. *Department of Structural and Functional Biology, and Centre of Neuroscience, University of Insubria, Busto Arsizio, Italy
      †Department of Neuroscience, University of Torino, Torino, Italy
      ‡Salvatore Maugeri Foundation, IRCCS , Pavia, Italy
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  • Bruno Bergamasco,

    1. *Department of Structural and Functional Biology, and Centre of Neuroscience, University of Insubria, Busto Arsizio, Italy
      †Department of Neuroscience, University of Torino, Torino, Italy
      ‡Salvatore Maugeri Foundation, IRCCS , Pavia, Italy
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  • and , Leonardo Lopiano

    1. *Department of Structural and Functional Biology, and Centre of Neuroscience, University of Insubria, Busto Arsizio, Italy
      †Department of Neuroscience, University of Torino, Torino, Italy
      ‡Salvatore Maugeri Foundation, IRCCS , Pavia, Italy
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Address correspondence and reprint requests to Professor Mauro Fasano, Department of Structural and Functional Biology, via Alberto da Giussano 12, 21052 Busto Arsizio, Italy.
E-mail: mauro.fasano@uninsubria.it

Abstract

Parkinson's disease is a common neurodegenerative disorder with a mainly sporadic aetiology, although a number of monogenic familiar forms are known. Most of the motor symptoms are due to selective depletion of dopaminergic, neuromelanin-containing neurones of the substantia nigra pars compacta. Neuromelanin is the dark insoluble macromolecule that confers the black (substantia nigra) or grey (locus coeruleus) colour to monoaminergic basal ganglia. In particular, nigral neurones are pigmented because of the accumulation of by-products of oxidative metabolism of the neurotransmitter dopamine. The occurrence of dopamine (and all the enzymatic machinery required for dopamine synthesis, re-uptake and disposal) and neuromelanin, and a large amount of iron ions that interact with them, makes dopaminergic nigral neurones peculiarly susceptible to oxidative stress conditions that, in turn, may become amplified by the iron–neuromelanin system itself. In this mini-review we describe biophysical evidence for iron–neuromelanin modifications that support this hypothesis. Furthermore, we discuss the formation of the covalent linkage between α-synuclein and neuromelanin from the early stages of the disease.

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